1. Field of the Invention
This invention relates to compounds having antineoplastic activity, i.e., activity for inhibiting the growth of malignant tumors. More specifically it relates to compounds of the class 2,3-bis(aziridinyl)-1,4-naphthoquinone sulfonate derivatives, an intermediate therefor, and the use of these compounds in inhibiting malignant tumors.
2. Prior Art and Other Information
Assignee herein has discovered other classes of compounds useful for inhibiting the growth of malignant tumors. These compounds are described in U.S. Ser. No. 06/683,852, filed on Dec. 20, 1984, and now abandoned, and also in U.S. Ser. No. 06/810,644 now U.S. Pat. No. 4,684,747, filed on Dec. 18, 1985, which is a continuation-in-part of U.S. Ser. No. 06/683,852. The compounds described in this application are also described in Shyam et al. J. Med. Chem., 28, 525 (1985). These compounds are N,N'-bis(sulfonyl)hydrazines and are particularly active against both L1210 leukemia and B16 melanoma. Additionally, Assignee herein has also discovered 1-alkyl-2-arenesulfonyl-2-methoxycarbonyl sulfenyl hydrazines which are also useful for inhibiting the growth of malignant tumors. These compounds are described in U.S. Ser. No. 820,114 filed on Jan. 21, 1986, now abandoned and refiled in U.S. Ser. No. 142,354 on Dec. 28, 1987 and have significant activity against mice bearing the B16 melanoma.
Additionally, Applicant is aware of several references which describe compounds which might be considered relevant to the invention described and claimed herein.
In particular, U.S. Pat. No. 2,868,782 to Gauss describes polyhydro-2-aziridino-1,4-naphthoquinones. These compounds have the formula: ##STR4## wherein R is a divalent radical selected from the group consisting of --CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 --, --CH.dbd.CHCH.sub.2 CH.sub.2 -- or --CH.sub.2 CH.dbd.CHCH.sub.2 -- and R' may be hydrogen or methyl. The compounds are described as useful in chemotherapy and more particularly possessing cytostatic properties useful in the study and treatment of cancer.
U.S. Pat. No. 3,631,026 to Nakao describes 2,5-bis(1-aziridinyl)-1,4-benzoquinone derivatives of the formula: ##STR5## The compounds are said to exert an antileukemic activity and may be used on human beings as a drug for the remission and treatment of leukemia.
U.S. Pat. No. 4,146,622 to Driscoll describes aziridinyl quinone type compounds of the formula: ##STR6##
The preferred compounds are 2,5-diaziridinyl-1,4-benzoquinone derivatives.
U.S. Pat. Nos. 4,418,078 and 4,540,519 both to Murdock describes 1,4-bis(substituted-amino)-5,8-dihydroxyanthraquinone compounds of the type: ##STR7## an aziridinyl substituent may be formed by R.sub.1 and R.sub.2. The compounds are said to be useful in inhibiting the growth of transplanted mouse tumors.
British Pat. No. 864,747 describes "alkyleneimino-quinones" of the formula: ##STR8## wherein X and Y may represent an "annelated pyridine or benzene nucleus" and R may be a hydrogen or methyl group. More specifically this reference describes "2,3-di-(ethylene-imino)-naphthoquinone-(1,4)". The compounds are described are capable of inhibiting the growth of animal tumor cells.
None of the foregoing references teach or suggest the compounds described and claimed herein.